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Journal of Cell Science 114, 3455-3462 (2001)
© 2001 The Company of Biologists Limited

RESEARCH ARTICLE

UV-induced binding of ING1 to PCNA regulates the induction of apoptosis

Michelle Scott1, Paul Bonnefin1, Diego Vieyra1, Francois-Michel Boisvert1, Dallan Young1,2, David P. Bazett-Jones1 and Karl Riabowol1,2,*

1 Departments of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada
2 Department of Oncology, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada

*Author for correspondence (e-mail: karl{at}ucalgary.ca)

Accepted June 15, 2001

Previous studies have shown that UV-induced binding of p21WAF1 to PCNA through the PCNA-interacting protein (PIP) domain in p21WAF1 promotes a switch from DNA replication to DNA repair by altering the PCNA protein complex. Here we show that the p33ING1b isoform of the ING1 candidate tumour suppressor contains a PIP domain. UV rapidly induces p33ING1b to bind PCNA competitively through this domain, a motif also found in DNA ligase, the DNA repair-associated FEN1 and XPG exo/endonucleases, and DNA methyltransferase. Interaction of p33ING1b with PCNA occurs between a significant proportion of ING1 and PCNA, increases more than tenfold in response to UV and is specifically inhibited by overexpression of p21WAF1, but not by p16MTS1, which has no PIP sequence. In contrast to wild-type p33ING1b, ING1 PIP mutants that do not bind PCNA do not induce apoptosis, but protect cells from UV-induced apoptosis, suggesting a role for this PCNA-p33ING1b interaction in eliminating UV-damaged cells through programmed cell death. These data indicate that ING1 competitively binds PCNA through a site used by growth regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of the PCNA protein complex.

Key words: Apoptosis, DNA damage, ING1, PCNA, PIP




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© The Company of Biologists Ltd 2001